Phase 2 Adaptive Trial Design to Evaluate
VS-6766 Alone and in Combination with Defactinib With a Focus on
KRAS-G12V Mutations
Trial Designed to Address Significant Unmet
Medical Need in These Treatment-Resistant Tumors
Verastem Oncology to Seek FDA Accelerated
Approval, Pending Trial Outcome
Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology),
a biopharmaceutical company committed to advancing new medicines
for patients battling cancer, today announced the initiation of a
Phase 2 registration-directed clinical trial of VS-6766, its
RAF/MEK inhibitor, alone and in combination with defactinib, its
FAK inhibitor, in patients with KRAS mutant non-small cell lung
cancer (NSCLC).
“Currently available options for patients with KRAS mutant NSCLC
are associated with minimal efficacy, as well as resistance and
toxicity issues. Our study will further elucidate the impact of
VS-6766, alone or in combination with defactinib, in overcoming
these challenges to improve outcomes,” said Brian Stuglik, Chief
Executive Officer of Verastem Oncology. “Our VS-6766 and defactinib
NSCLC development program’s specific focus on G12V mutations is
unique and represents a potentially significant step forward in
understanding how we can deliver a better treatment option for
these patients.”
The RAMP 202 (Raf And Mek Program)
study is a Phase 2, adaptive two-part multicenter, parallel cohort,
randomized, open-label trial to evaluate the efficacy and safety of
VS-6766 alone and in combination with defactinib in patients with
KRAS mutant NSCLC, following treatment with a platinum-based
regimen and immune checkpoint inhibitor.1 The first part of the
study will determine the optimal regimen of either VS-6766
monotherapy or in combination with defactinib in patients with
KRAS-G12V mutant NSCLC randomized 1:1 in each treatment arm. An
exploratory arm of the initial phase of the study will evaluate
other KRAS mutations. The determination of which regimen to take
forward into the expansion phase of the trial will be made based on
data from KRAS-G12V mutant patients. The second phase of the study
will examine efficacy and safety parameters of the most effective
regimen. Additional information about this study can be found here
on ClinicalTrials.gov (NCT04620330).
“In this study, we hope to advance our understanding of a
potential new option for patients with KRAS mutant NSCLC by
targeting the RAF/MEK and FAK pathways,” said D. Ross Camidge,
M.D., Ph.D., Director of Thoracic Oncology at the University of
Colorado School of Medicine and University of Colorado Cancer
Center member and the study’s U.S. principal investigator. “Some
key advances have come from looking at specific KRAS mutations and
by also focusing on G12V mutations, allowing us to build upon the
areas that have shown particular promise and determine an optimal
path forward.”
“NSCLC, which constitutes over 80% of lung cancers,2 is the
single leading cause of cancer deaths worldwide2 and approximately
25% of NSCLCs contain activating mutations in the RAS signaling
pathway,”3 said Silvia Novello, M.D., Ph.D., Professor of
Respiratory Medicine at the Department of Clinical and Biological
Sciences of the University of Turin, Italy and EU principal
investigator of the study. “Making progress with these mutated
tumors is critical as they have proven extremely difficult to
target with an effective and well-tolerated option and have,
therefore, left patients with limited options and minimal
results.”
Verastem Oncology recently announced the initiation of its RAMP
201 Phase 2 registration-directed clinical trial of VS-6766 and
defactinib, in patients with recurrent low-grade serous ovarian
cancer.
About KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)
Approximately 85% of lung cancers are non-small cell lung cancer
(NSCLC),2 which are the single leading cause of cancer deaths
worldwide.2 KRAS mutation occurs in approximately 25% of NSCLC
adenocarcinoma patients.3 Two of the most common types of KRAS
mutations are G12V, which are present in approximately 7% of NSCLC
and G12C,4 which occur in approximately 13% of NSCLCs.5 There are
several agents in development for KRAS-G12C mutations, but this
study represents the first time that an agent will be studied
specifically for KRAS-G12V. Studies suggest that these types of
KRAS mutations differ in clinical characteristics and response to
traditional treatments such as chemotherapy.6
About VS-6766
VS-6766 is an oral small molecule inhibitor of the RAF/MEK
signaling pathway. In contrast to other MEK inhibitors in
development, VS-6766 blocks both MEK kinase activity and the
ability of RAF to phosphorylate MEK. This unique mechanism allows
VS-6766 to block MEK signaling without the compensatory activation
of MEK that appears to limit the efficacy of other inhibitors.
About Defactinib
Defactinib (VS-6063) is an oral small molecule inhibitor of the
FAK and PYK2 signaling pathways that is currently being evaluated
as a potential combination therapy for various solid tumors.
Verastem Oncology has received Orphan Drug Designation for
defactinib in ovarian cancer in the U.S., EU and Australia.
Preclinical research by Verastem Oncology scientists and
collaborators at world-renowned research institutions have
described the effect of FAK inhibition to enhance immune response
by decreasing immuno-suppressive cells, increasing cytotoxic T
cells, and reducing stromal density, which allows tumor-killing
immune cells to enter the tumor.7,8
About the VS-6766/Defactinib Combination
RAS mutant tumors are present in about 30% of all human cancers,
have historically presented a difficult treatment challenge and are
often associated with significantly worse prognosis.9 Challenges
associated with identifying new treatment options for these types
of cancers include resistance to single agents,9 identifying
tolerable combination regimens with MEK inhibitors and new RAS
inhibitors in development addressing only a minority of all RAS
mutated cancers.
The combination of VS-6766 and defactinib has been found to be
clinically active in patients with KRAS mutant tumors. In an
ongoing investigator-initiated Phase 1/2 FRAME study, the
combination of VS-6766 and defactinib is being evaluated in
patients with recurrent low-grade serous ovarian cancer (LGSOC),
KRAS mutant NSCLC and colorectal cancer. Updated data from this
study presented at the 2nd Annual RAS-Targeted Drug Development
Summit in September 2020 demonstrated a 56% overall response rate
and long duration of therapy among patients with KRAS-G12 mutant
LGSOC.10 Based on an observation of higher response rates seen in
NSCLC patients with KRAS-G12V mutations in the study, Verastem
Oncology is also exploring the role of VS-6766 and defactinib in
KRAS-G12V mutant NSCLC in its Phase 2 RAMP 202 (Raf
And Mek Program) study. The FRAME study was
expanded in August 2020 to include new cohorts in pancreatic
cancer, KRAS mutant endometrial cancer and KRAS-G12V mutant
NSCLC.
About Verastem Oncology
Verastem Oncology (Nasdaq:VSTM) is a development-stage
biopharmaceutical company committed to the development and
commercialization of new medicines to improve the lives of patients
diagnosed with cancer. Our pipeline is focused on novel small
molecule drugs that inhibit critical signaling pathways in cancer
that promote cancer cell survival and tumor growth, including
RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition. For
more information, please visit www.verastem.com.
Forward-Looking Statements Notice
This press release includes forward-looking statements about
Verastem Oncology’s strategy, future plans and prospects, including
statements related to the potential clinical value of the
RAF/MEK/FAK combination and the timing of commencing a
registration-directed trial for the RAF/MEK/FAK combination. The
words "anticipate," "believe," "estimate," "expect," "intend,"
"may," "plan," "predict," "project," "target," "potential," "will,"
"would," "could," "should," "continue," “can,” “promising” and
similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. Each forward-looking statement is subject
to risks and uncertainties that could cause actual results to
differ materially from those expressed or implied in such
statement.
Applicable risks and uncertainties include the risks and
uncertainties, among other things, regarding: the success in the
development and potential commercialization of our product
candidates, including defactinib in combination with VS-6766; the
occurrence of adverse safety events and/or unexpected concerns that
may arise from additional data or analysis or result in
unmanageable safety profiles as compared to their levels of
efficacy; our ability to obtain, maintain and enforce patent and
other intellectual property protection for our product candidates;
the scope, timing, and outcome of any legal proceedings; decisions
by regulatory authorities regarding labeling and other matters that
could affect the availability or commercial potential of our
product candidates; whether preclinical testing of our product
candidates and preliminary or interim data from clinical trials
will be predictive of the results or success of ongoing or later
clinical trials; that the timing, scope and rate of reimbursement
for our product candidates is uncertain; that third-party payors
(including government agencies) may not reimburse; that there may
be competitive developments affecting our product candidates; that
data may not be available when expected; that enrollment of
clinical trials may take longer than expected; that our product
candidates will experience manufacturing or supply interruptions or
failures; that we will be unable to successfully initiate or
complete the clinical development and eventual commercialization of
our product candidates; that the development and commercialization
of our product candidates will take longer or cost more than
planned; that we or Chugai Pharmaceutical Co., Ltd. will fail to
fully perform under the VS-6766 license agreement; that we may not
have sufficient cash to fund our contemplated operations; that we
may be unable to make additional draws under our debt facility or
obtain adequate financing in the future through product licensing,
co-promotional arrangements, public or private equity, debt
financing or otherwise; that we will be unable to execute on our
partnering strategies for defactinib in combination with VS-6766;
that we will not pursue or submit regulatory filings for our
product candidates; and that our product candidates will not
receive regulatory approval, become commercially successful
products, or result in new treatment options being offered to
patients.
Other risks and uncertainties include those identified under the
heading “Risk Factors” in our Quarterly Report on Form 10-Q for the
quarter ended September 30, 2020 as filed with the Securities and
Exchange Commission (SEC) on November 9, 2020 and in any subsequent
filings with the SEC. The forward-looking statements contained in
this press release reflect Verastem Oncology’s views as of the date
hereof, and we do not assume and specifically disclaim any
obligation to update any forward-looking statements whether as a
result of new information, future events or otherwise, except as
required by law.
References
________________________ 1 Clinicaltrials.gov. A Study of
VS-6766 v. VS-6766 + Defactinib in Recurrent G12V or Other
KRAS-Mutant Non-Small Cell Lung Cancer. Available at:
https://clinicaltrials.gov/ct2/show/NCT04620330?term=VS-6766&draw=2&rank=2.
Accessed December 15, 2020. 2 Molina, Julian R., Non–Small Cell
Lung Cancer: Epidemiology, Risk Factors, Treatment, and
Survivorship. National Institute of Health. Mayo Foundation for
Medical Education and Research. Available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718421/pdf/nihms121782.pdf.
Accessed December 15, 2020. 3 Roman, Marta, et al. KRAS oncogene in
non-small cell lung cancer: clinical perspectives on the treatment
of an old target. Molecular Cancer (2018) 17:33. 4 TCGA PanCancer
Atlas (cBioPortal analysis) 5 American Cancer Society. Key
Statistics for Lung Cancer. Available at:
https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html.
Accessed December 15, 2020. 6 Garassino, M. C. et al. Different
types of K-Ras mutations could affect drug sensitivity and tumour
behaviour in non-small-cell lung cancer. Annals of Oncology. 2011
Jan;22(1):235-237. doi: 10.1093/annonc/mdq680. PMID: 21169473. 7
Chénard-Poirier, M. et al. Results from the biomarker-driven basket
trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor, in RAS-
or RAF-mutated malignancies including multiple myeloma. Journal of
Clinical Oncology 2017: 35. 10.1200/JCO.2017.35.15_suppl.2506. 8
ClinicalTrials.gov. Phase I Trial of VS-6063 and RO5126766.
(FRAME). Available at:
https://clinicaltrials.gov/ct2/show/NCT03875820. Accessed December
15, 2020. 9 Baines, A. T., Xu, D., & Der, C. J. (2011).
Inhibition of Ras for cancer treatment: the search continues.
Future medicinal chemistry, 3(14), 1787–1808.
https://doi.org/10.4155/fmc.11.121 10 Verastem Oncology Press
Release. Verastem Oncology Announces Presentation of Updated Phase
1/2 FRAME Study Data at the 2nd Annual RAS-Targeted Drug
Development Summit. September 16, 2020. Available at:
https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-announces-presentation-updated-phase-12-frame.
Accessed December 15, 2020.
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version on businesswire.com: https://www.businesswire.com/news/home/20201215005318/en/
Investors: Ajay Munshi VP, Corporate Development +1 781-469-1579
amunshi@verastem.com
Media: Lisa Buffington VP, Corporate Communications +1
781-292-4205 lbuffington@verastem.com
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